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While cancerous cells look a lot like normal human cells, they're still different enough that the immune system regularly attacks them. Obviously, this attack sometimes bogs down, allowing cancer to thrive and spread. Figuring out how to get the immune system back on track has been a major focus of research, and success in the area has been honored with a Nobel Prize.

Despite these successes, many patients aren't helped by the newer immune-focused therapies, raising questions of what else we still need to figure out to help cancer patients. A new paper highlights something we may have missed: a class of immune cells that appears to be primed specifically to attack cancer. But the finding raises questions about what it is on cancer cells that the immune cells are recognizing and why they fail to keep cancer in check.

Finding cancer killers

The start of this work was pretty simple: a large international team of researchers grew a mix of immune cells called "T cells" in the presence of cancerous cells and looked for cells that grew rapidly. This rapid growth is typically a sign that the immune cells have been activated by something they recognize—in this case, the cancer. They identified one particular lineage of T cells that grew well and named it MC.7.G5, confirming yet again that most scientists don't belong in the creative industries.

One notable thing about the MC.7.G5 cells quickly became apparent: MC.7.G5 didn't simply grow well in the presence of cancer cells; it killed them. So, the authors tested a variety of different cancer types (lung cancer, melanoma, colon, breast, and more). These cells don't have much in common. They're activated by different mutations, start out with different populations of proteins on their surface, and have many other differences from one another. So it wasn't clear what the T cells could possibly be recognizing on their surfaces in order to attack them. Yet attack them they did.

To find out, the researchers did an experiment that wouldn't have been possible just a decade earlier: they used a gene-editing construct to eliminate every single protein-coding gene that we know of in the genome. Lots of individual populations of a cancer-cell line had a single gene knocked out and then were tested to see whether the MC.7.G5 immune cells could still kill them. If any cancer cells were left alive, then the gene edited in them would be essential for producing the molecule used by the immune cells to recognize cancer.

Further Reading

The experiment identified a series of genes involved in putting a single protein on the surface. But, of course, that protein is also present on normal cells. How could it possibly be responsible for the cancer cells being recognized as distinct?

Fortunately, we know a lot about the family of molecules that the protein, MR1, belongs to, as well as a bit about MR1 itself. The larger family includes the molecules that help the immune system recognize self from non-self by binding to bits of the cell's proteins and presenting them on the cell's surface for the immune system to check out. If either these molecules or the proteins they present look different, the immune system attacks. So, that makes a degree of sense as something that can trigger the immune system to go after the cancer cells.

MR1, however, doesn't work like that. Instead, it brings some of the cell's metabolites to the surface. And the researchers confirmed that it has to bind to something in order to make it to the surface. They hypothesize that it's a metabolite that's specific to cancer cells, but they have no idea what it might be.

Stay on target

While there are still some question marks about what causes these immune cells to pick out cancerous cells, there's no shortage of evidence that they do so effectively. The researchers tested the immune cells against resting and dividing normal cells and got no response. MC.7.G5 didn't kill healthy cells that were stressed or damaged. So, there's no indication that the immune cells accidentally go off target and kill healthy cells.

The researchers also confirmed that the cancer-killing T cells are defined by the standard receptor that T cells normally use to recognize infected cells. They made a copy of this receptor's genes and inserted them into T cells from an unrelated individual. They also killed cancerous cells from at least two different sources.

Finally, the authors injected lymphoma cells into immune-compromised mice, then added the cancer-killing T cells. In control mice without the cancer-killing cells, the lymphoma took over the bone marrow, eventually accounting for about 80 percent of the cells there. With the cancer-killing cells injected at the same time, the bone marrow in the mice consistently had far fewer cancer cells (consistently less than 10 percent of the total cells). This indicates that the immune cells can help keep cancer in check but may not be able to consistently eradicate it.

Does that mean, as the BBC has claimed, that these cells "May treat all cancer"? Well, to begin with, the T cells were seemingly unable to eliminate cancer in mice. That's more significant than it seems, in that lots of potential treatments seem to work well in mice, but few ever advance to the point of clinical trials in humans, much less end up being used as treatments. This is a case when mouse assays are helpful for knowing what deserves a closer look but far from the last word on a topic.

Do we all have cancer killers?

These cancer-killing immune cells were also obtained from at least two individuals, suggesting that they may be present in all humans. Yet humans regularly suffer from cancer, so there's clearly something that keeps them from doing their job. At this point, we don't have the slightest clue as to what that something might be.

Then there's the issue of what the cells are recognizing that allows them to identify cancer cells. Whatever it is, it's not widely present on healthy cells. But the body has a dizzying number of specialized cell types, so we've barely scratched the surface of testing whether these cells might attack some healthy cell types. However, if the authors are right about a couple of things, there's a very good chance the cells might.

The authors suggest that the target of the cancer-killing cells is a metabolite presented on the surface by the protein MR1. And, because the gene-editing screen didn't pull out any metabolic enzymes, they suspect that the metabolite is essential for cancer cell viability. It's difficult to understand how something central to cancer cell viability, produced using the same genes found in normal cells, isn't ever produced by normal cells.

None of this is to say that this discovery won't end up being important. But we really need much more information before we're in a position to judge whether it is or not.

I saw all the headlines in the news a couple days ago, and after a brief moment of hopeful glee, suppressed it, and then avoided reading anything. I figured that with that much coverage, in a couple days Ars would probably publish a well thought out piece that explains the nuance of what this research really discovered, the current context of the field, and why it may be promising but also why it may lead nowhere in terms of viable treatment (like so many other promising avenues of research before it).

So thanks for continuously proving me right, it's been a real time saver

As a biologist I just wanted to thank Ars for producing a good write up on this research. It's so frustrating to see legitimate news outlets butcher science reporting over and over again. Reading this write up is a breath of fresh air compared to the hack job done by the BBC earlier this week.

This is very cool and important research. It doesn't need exaggeration to make it cool. I wish more science journalists appreciated that fact like John does.

Looks extremely promising from everything I've read, but there are also experiments going on with anti-CD47 and anti-CD24 there are much further along. Hopefully one gets us to a breakthrough treatment.

They identified one particular lineage of T cells that grew well and named it MC.7.G5, confirming yet again that most scientists don't belong in the creative industries.

Science is serious stuff. Besides, considering how many people like to claim "junk science" when they don't agree with it, probably wouldn't be a good idea to be punny.

I am very much looking forward to seeing how this discovery develops.

I'm fairly certain science deniers and their foul ilk don't care if we call things "up, down" or "strange, charm" quarks, they hate it all the same. Climatology doesn't have many "punny" names involved, and it's a favorite target. I don't think calling things pithier or more clever names than MC.7.G5 is going to change the minds* of those poor sods.

They identified one particular lineage of T cells that grew well and named it MC.7.G5, confirming yet again that most scientists don't belong in the creative industries.

Science is serious stuff. Besides, considering how many people like to claim "junk science" when they don't agree with it, probably wouldn't be a good idea to be punny.

Plus it's fairly straightforward understand the name. The paper mentions a screen, screens are done with high throughput and hopefully automation - so they are using 96 or 384 well plastic plates to grow their cultures in. G5 is most certainly the row/column in that plastic plate (rows labeled A-H or A- P, columns 1-12 or 1-24). 7 would most likely indicate that the hit came up on the 7th plate - leaving us to ponder the MC designation. And here we enter guessing territory - it could be the initials of the first author (Michael Crowther), because if you label your lab materials you kinda go with the simplest option.

Voila: MC.7.G5 - initials.plate.plate_position

On second thought, this might argue against the use of automation, because then there should be barcodes instead of initials.

Attacking a cancer cell isn't what we need to treat the disease. KILLING it is.

To put it into perspective in a more mundane fashion, think of a T-cell as a soldier using a .22 rifle to attack a tank. It's attacking it, but the tank doesn't really care. Light armor vehicles might care more, so some "cancers" are impacted more than others.

How well they work in killing the cancer is what they need to find out. That it attacks them is useful information. But it may ultimately be pointless if the cancer cells aren't otherwise destroyed in the attack.

To extend the analogy further, if a soldier carrying a .22 can get inside a tank, the tank is rendered useless when the crew (or metabolism) of the tank is destroyed. Then they can drop a grenade and destroy the tank from the inside. Using these kind of mechanisms to get inside a cancer cell and destroy it might be more effective than using T-cells alone. Figuring out whether or not adding a .22 or hand grenade to a T-cell will be effective, or even possible, takes a lot of work, and has a lot of unknowns.

Until that's determined, the usefulness of this knowledge is limited to the kind of research they're doing now. It'll be a while before we see clinical trials from anything learned in this insight.

We already have actual treatments that have a lot of unknowns, that really isn't an obstacle. For example, treating bladder cancer with BCG is standard practice but the mechanism of action isn't really clear.

And there have been decades of work in melanoma in getting a patients T-cells, growing them in a lab, and putting them back in the patient. Works fabulously for some patients and not at all for others, but is a viable option as a treatment. So a lot of the basic procedures are largely worked out.

For something this promising, it may be closer to the clinic than you would think.

I saw all the headlines in the news a couple days ago, and after a brief moment of hopeful glee, suppressed it, and then avoided reading anything. I figured that with that much coverage, in a couple days Ars would probably publish a well thought out piece that explains the nuance of what this research really discovered, the current context of the field, and why it may be promising but also why it may lead nowhere in terms of viable treatment (like so many other promising avenues of research before it). So thanks for continuously proving me right, it's been a real time saver

After reading this article, reading your comment, and realizing how I feel the same way every time I read an article on Ars Technica, I went ahead and subscribed. Thanks for putting your thoughts into words and saying what I was thinking too!

Cancer is Goldblums "Life, uh, finds a way" attempt at reversion back to the single cell milieu. Usually unsuccessful from an evolutionary standpoint but exceptions include HeLa, Tasmanian Devil cancer and the sexually transmitted canine cancer.

My father has stage 4 cancer. It is painful to see all these discoveries that will be too little too late to help him. But, at least it will be a great resource for future families.

I am sorry.

I don't know if it is solace, but discoveries like these are great and amazing, but we still haven't "cured" cancer yet. Maybe someone will tomorrow, but experience seems to be we end up learning something new and chipping away at it. Cancer survival rates continue to get better and better, but it hasn't been by leaps and bounds. Its a percent or two here, a percent or two there who undergo complete remission through advances in cancer treatment. Maybe a few extra weeks here and there every once in awhile.

I wish and hope someone invents a cure today, but it is unlikely to be "just missed".

If I were to take a wild ass guess, what might be the most helpful (supposing we never do come up with "this one foolproof trick to beat cancer") is a reliable method, that is relatively non-invasive and inexpensive for screening.

Example, a pin prick test that could screen for all cancer types with high accuracy that might cost a few bucks to run so you can test yourself monthly or something and then get treatment at very, very, very early stage 1. I understand the improbability of that (and that circulating cancer cells wouldn't be stage 1), but I can hope that some day we can move towards detecting cancers extremely early as the vast, vast majority of them can be successfully treated to full remission if caught early.

I've lost a grandfather to prostate cancer that was extremely aggressive in his early 70s. My other grandfather developed prostate cancer at a relatively young age (mid 60s), had it removed. Later developed bladder cancer in his early 80s (80, 81yrs old he was diagnosed?) and lived about 18 months with it. My dad developed testicular cancer when he was 44, surgery and radiation and has been in remission since. One of my grand uncles died of prostate cancer also (though he at least made it to 91. So at that point, kind of a toss up on what kills you).

My outlook doesn't look all that rosy...

And that is just with my familial reproductive parts. My aunt died from thyroid cancer at age 70. My mother has parathyroid disease and is in her late 60s and has been dragging her feet on getting surgery to treat it (parathyroid disease is often caused by non-aggressive tumor of the parathyroid. Won't know unless or until my mother has her parathyroid removed). My dad had a lymph node tumor removed when he was in his early teens.

At least the last few generations, its generally been cancer that has killed my family members. Hell, my brother is a super rare exception where it was pneumonia he refused to get treated that killed him at age 41.

Then again, if you go back a generation further to my great grandparent's generation, it was all strokes and heart attacks in their 50s and 60s that mostly killed them from smoking, drinking too much, working in the mines or other hazardous work. Though my great grandmothers mostly lived up in to their 90s. And suffered Alzheimer's or dementia for the last ~10 years of their life (just like my grandmothers, though they only lasted till their mid 80s).

I know something's going to get you, but it looks like cancer is probably going to be what gets me. So if we can figure something out for that...that'd be real swell (though then maybe I'd just end up a mental vegetable for most of my 80s and early 90s. So if we can fix that one too...)

Cancer research reminds me of nuclear fusion research: tons of money, time, expertise and energy is put into an eventual breakthrough solution that never seems to really happen. Of course, there are many types of cancer, and each one really is its own disease from a curative standpoint.. I realize that progress is being made in treating many types of cancer, but that's little consolation to the millions of people dying from cancer at this very moment. Articles like this are nice for arm-chair scientists to ponder over, but its worthless nonsense for an actual, suffering patient.

Likewise, there have been some very significant breakthroughs with fusion energy in recent years.. but its ALWAYS a decade, or more, until we see practical application. Little consolation to a burning planet, choking itself on fossil fuels. We need it now. 2040 or whatever will be too little, too late.

Cancer and fusion energy: put up or shut up.

What an idiotic comparison. As you correctly noted cancer is a large family of somewhat related diseases. From virtually none of them being ever curable 100 years ago, we have got to about 50% of them curable by surgery, chemo and radiation, and only very few where you are no better off than 100 years ago. I have a brother who already has over 45 years of extra life thanks to a drug for a cancer which was completely incurable 10 years earlier. Over the next five years I expect even KRAS tumors to respond to the new paradigms, and I am excited to see this.

Cancer research reminds me of nuclear fusion research: tons of money, time, expertise and energy is put into an eventual breakthrough solution that never seems to really happen. Of course, there are many types of cancer, and each one really is its own disease from a curative standpoint.. I realize that progress is being made in treating many types of cancer, but that's little consolation to the millions of people dying from cancer at this very moment. Articles like this are nice for arm-chair scientists to ponder over, but its worthless nonsense for an actual, suffering patient.

Likewise, there have been some very significant breakthroughs with fusion energy in recent years.. but its ALWAYS a decade, or more, until we see practical application. Little consolation to a burning planet, choking itself on fossil fuels. We need it now. 2040 or whatever will be too little, too late.

Cancer and fusion energy: put up or shut up.

So, wait, if we can't cure all cancers now, we should stop all research now? That's... ridiculous, to put it mildly.

Cancer research reminds me of nuclear fusion research: tons of money, time, expertise and energy is put into an eventual breakthrough solution that never seems to really happen. Of course, there are many types of cancer, and each one really is its own disease from a curative standpoint.. I realize that progress is being made in treating many types of cancer, but that's little consolation to the millions of people dying from cancer at this very moment. Articles like this are nice for arm-chair scientists to ponder over, but its worthless nonsense for an actual, suffering patient.

Likewise, there have been some very significant breakthroughs with fusion energy in recent years.. but its ALWAYS a decade, or more, until we see practical application. Little consolation to a burning planet, choking itself on fossil fuels. We need it now. 2040 or whatever will be too little, too late.

Cancer and fusion energy: put up or shut up.

Bad analogy.Fusion research has yet to deliver anything that looks like a product; cancer research is increasing life expectancy, in dribs and drabs admittedly, but it is happening.

This is a very interesting paper. It does not offer a cancer cure on a plate, but quite possibly insight to a system of cancer suppression that we did not previously realize exists. Clearly it can fail, or we would not get cancer, but as we learn when it works and when it fails, why it fails, we may well gain the insight to a whole new series of attacks on the disease, and ones which may well prove to be orthogonal to what we already do, and hence be used in an additive mode.

The authors suggest that the target of the cancer-killing cells is a metabolite presented on the surface by the protein MR1. And, because the gene-editing screen didn't pull out any metabolic enzymes, they suspect that the metabolite is essential for cancer cell viability. It's difficult to understand how something central to cancer cell viability, produced using the same genes found in normal cells, isn't ever produced by normal cells.

What if it's the other way round – the metabolite is produced by all normal cells but not cancer cells? It might be involved in a mechanism that keeps cells from dividing uncontrollably. MR1 presents the metabolite and says "see, my growth control is working". If the control mechanism breaks down, then the cell starts dividing, but then the metabolite isn't produced, and MC.7.G5 sees that it's missing, and attacks. Seems possible to me.

Cancer research reminds me of nuclear fusion research: tons of money, time, expertise and energy is put into an eventual breakthrough solution that never seems to really happen. Of course, there are many types of cancer, and each one really is its own disease from a curative standpoint.. I realize that progress is being made in treating many types of cancer, but that's little consolation to the millions of people dying from cancer at this very moment. Articles like this are nice for arm-chair scientists to ponder over, but its worthless nonsense for an actual, suffering patient.

Likewise, there have been some very significant breakthroughs with fusion energy in recent years.. but its ALWAYS a decade, or more, until we see practical application. Little consolation to a burning planet, choking itself on fossil fuels. We need it now. 2040 or whatever will be too little, too late.

Cancer and fusion energy: put up or shut up.

Bad analogy.Fusion research has yet to deliver anything that looks like a product; cancer research is increasing life expectancy, in dribs and drabs admittedly, but it is happening.

Even drib and drabs can make a difference. Show me a drug or treatment that buys six months, and I will find some patients who lived another five years.

Cancer research reminds me of nuclear fusion research: tons of money, time, expertise and energy is put into an eventual breakthrough solution that never seems to really happen. Of course, there are many types of cancer, and each one really is its own disease from a curative standpoint.. I realize that progress is being made in treating many types of cancer, but that's little consolation to the millions of people dying from cancer at this very moment. Articles like this are nice for arm-chair scientists to ponder over, but its worthless nonsense for an actual, suffering patient.

Likewise, there have been some very significant breakthroughs with fusion energy in recent years.. but its ALWAYS a decade, or more, until we see practical application. Little consolation to a burning planet, choking itself on fossil fuels. We need it now. 2040 or whatever will be too little, too late.

Cancer and fusion energy: put up or shut up.

What are you even babbling about? They aren't remotely the same thing.

Fusion is effectively binary. It either is, or is not working fusion (by working I mean >break even).

Cancer treatment research isn't "cure all the cancers, or nothing".

The state of the art/medicine advances bits and pieces. 60 years ago, my Dad would have died of testicular cancer probably. 15 years ago when my one friend died of testicular cancer (diagnosed at stage 3, my Dad's was diagnosed at stage 1), it might have been treatable to remission today. 30 years ago, you probably would die of breast cancer if you were diagnosed with it. Now between more frequent screening, better screening and massively better treatment options, most people who are diagnosed with breast cancer progress to full remission. Almost every cancer type, stage, etc. has SOME kind of treatment that is more advanced and better today than 20 years ago. In some cases it might only be the difference of a few weeks of extra life. In others it means remission.

These articles, at least as reported by Ars and some of the serious science publications (when they are doing their due diligence) aren't reporting "miracle break through". That is doing a disservice. They are reporting on interesting results. The scientists haven't claimed a cure. Or even something that can be tested in clinical trials. They are reporting a "oh, that's really interesting."

Because it IS important. It might lead no where, but they found something interesting and something interesting deserves them and others to try a bunch of different things to see if someone else comes up with the next interesting thing, about the interesting thing the first researchers found. At some point some researchers might develop a "cancer cure" from that having stood on the shoulders of all of those other researchers who found something interesting before them on up the chain to real revolutionary break through. But a break through rarely happens with one swing of the pick axe.

While articles like this are interesting fuel for rainy day woolgathering, there is one hardcore reality to face when discussing cancer.

A large percentage of cancer is self inflicted due a variety of lifestyle choices: smoking, drinking, diet, obesity, sun exposure and a whole host of other things. Humans have become quite adept at slowly killing themselves and then bemoaning the fact that they are dying.

A large percentage, sure.

Most appears to be a combination of hereditary as well as environmental. Heck, we are learning more and more than many are triggered by viruses (which might also have a hereditary influence on susceptibility). Those you typically don't have control over. Even if many of them are life style, go take a hike. We don't need any "they did it to themselves" mind think.

Next you are going to go piss on a homeless guy because all he has to do is pull himself up by his bootstraps.

Cancer research reminds me of nuclear fusion research: tons of money, time, expertise and energy is put into an eventual breakthrough solution that never seems to really happen. Of course, there are many types of cancer, and each one really is its own disease from a curative standpoint.. I realize that progress is being made in treating many types of cancer, but that's little consolation to the millions of people dying from cancer at this very moment. Articles like this are nice for arm-chair scientists to ponder over, but its worthless nonsense for an actual, suffering patient.

Likewise, there have been some very significant breakthroughs with fusion energy in recent years.. but its ALWAYS a decade, or more, until we see practical application. Little consolation to a burning planet, choking itself on fossil fuels. We need it now. 2040 or whatever will be too little, too late.

Cancer and fusion energy: put up or shut up.

Are you fucking kidding?

One of these things is for a power source. There are plenty of alternatives for power sources. The other is to cure a disease. "Put up or shut up" on finding a disease cure? What kind of timeline do you even put on something like that?

Of course this particular piece of research won't help people who are terminally ill right now. So that means we should just stop altogether, throw up our hands and say 'fuck it' because we can't fix it all right now today after decades of research? Despite the fact that progress is being and has been made? Despite the fact that research has already led to us being able to put many types of cancer into remission? What kind of attitude is this?

This is up there among some of the most obtuse takes I've ever seen on this site. I think nearly everyone, everywhere agrees with and supports research for finding a cure for cancer. Like, this might be one of the only issues on Earth that the majority of Democrats, Republicans, climate scientists, climate deniers, ICEV enthusiasts, BEV enthusiasts, pro-vaxxers and anti-vaxxers all agree we should pursue.

But you have to be the one person standing apart saying, "Nope. We've had enough time. Pack it in, we're done here."

Honestly, this is wonderful news. As someone who regularly donates to cancer research, I am always encouraged when I read about potential breakthroughs. No, they don't all pan out. But the fact that alternatives are being pursued, progress is being made, and new learning is always occurring is encouraging and altogether a good thing in my (and I suspect most peoples') opinion.

It might be useful, but if it depends on just one receptor then cancer cells can probably mutate around it.

Cancer isn't a foreign organism though or a virus that propagates... (though some cancer is triggered by them). So... any mutation occurs slowly over the generations of humans.

Of course mutation can occur from generation to generation in the cancer cells but mutating around this seems unlikely... in that case.

Cancer is a foreign organism that propagates. Unfortunately, it was originally part of you before it became foreign. That's why it's so hard to kill: most things that kill cancer will also kill you.

And mutations occur frequently in cancer, in part because the mechanisms that repair mutations and eliminate mutated cells are often broken in cancer cells. That's another reason cancer is hard to cure: many therapies will kill most of the cells in a tumor, but because the mutation rate is high, it's likely that the tumor will contain some resistant cells.

Cancer research reminds me of nuclear fusion research: tons of money, time, expertise and energy is put into an eventual breakthrough solution that never seems to really happen. Of course, there are many types of cancer, and each one really is its own disease from a curative standpoint.. I realize that progress is being made in treating many types of cancer, but that's little consolation to the millions of people dying from cancer at this very moment. Articles like this are nice for arm-chair scientists to ponder over, but its worthless nonsense for an actual, suffering patient.

Likewise, there have been some very significant breakthroughs with fusion energy in recent years.. but its ALWAYS a decade, or more, until we see practical application. Little consolation to a burning planet, choking itself on fossil fuels. We need it now. 2040 or whatever will be too little, too late.

Cancer and fusion energy: put up or shut up.

Bad analogy.Fusion research has yet to deliver anything that looks like a product; cancer research is increasing life expectancy, in dribs and drabs admittedly, but it is happening.

Honestly, this is wonderful news. As someone who regularly donates to cancer research, I am always encouraged when I read about potential breakthroughs. No, they don't all pan out. But the fact that alternatives are being pursued, progress is being made, and new learning is always occurring is encouraging and altogether a good thing in my (and I suspect most peoples') opinion.

As someone who quietly earmarks most of their United Way contribution to American Cancer Society, I'm interested if this astute forum has any advice on how to better contribute to fundamental research.

A lot of chemotherapy treatments wreak havoc on the immune system, even while killing lots of cancer cells. Maybe an alternating treatment between T-cells and chemo would be more effective than chemo by itself?

They identified one particular lineage of T cells that grew well and named it MC.7.G5, confirming yet again that most scientists don't belong in the creative industries.

Science is serious stuff. Besides, considering how many people like to claim "junk science" when they don't agree with it, probably wouldn't be a good idea to be punny.

I am very much looking forward to seeing how this discovery develops.

I'm fairly certain science deniers and their foul ilk don't care if we call things "up, down" or "strange, charm" quarks, they hate it all the same. Climatology doesn't have many "punny" names involved, and it's a favorite target. I don't think calling things pithier or more clever names than MC.7.G5 is going to change the minds* of those poor sods.

* The term mind with regards to reality denialists is used advisedly.

I notice you carefully avoided referencing top/truth and bottom/beauty quarks.